tbuckley/cabot-search huggingface dataset:
Clinical characteristics and treatment outcomes in patients with intracranial germ cell tumors: A single center analysis of 1448 patients in China.
Authors: Bo Li, Xiaoguang Qiu
Journal: Journal of Clinical Oncology (2022)

e14048 Background: To explore the clinical characteristics and treatment outcomes of patients with intracranial germ cell tumors (iGCTs). Methods: Clinical data of 1448 patients who were diagnosed with iGCTs based on histology and/or tumor marker elevation between 1990 and 2019 at Beijing Tiantan Hospital were studied retrospectively. Results: The median age was 12 years, and 74.3% of patients were male. In total, 32.6% of patients were of sellar origin, 32.3% were of pineal origin, 20.4% were of basal ganglia (BG) origin, and 14.7% were others. In nonmetastatic germinoma patients, multivariate analysis found that both whole-brain radiotherapy (p &lt; 0.001) and craniospinal irradiation (p = 0.040) could significantly reduce the risk of relapse compared with focal radiotherapy. In nonmetastatic NGGCT patients, the disease control rate was similar among the above three radiation volumes. Among 87 relapsed patients, those with germinoma (n = 35) showed a significantly higher out-field relapse rate than patients with NGGCTs (54.3% vs. 32.7%, p = 0.003). In patients with NGGCTs (n = 52), the in-field (36.5%) and out-field (32.7%) relapse rates were similar. In terms of relapse sites, relapse at the parenchyma (36.4%) was documented only in patients with BG region involvement. In patients with sellar or pineal origin, &gt; 80% of relapses were documented in ventricles and/or the spine. Conclusions: iGCT patients in our series showed unique characteristics. Considering both efficacy and potential adverse effects, the optimal radiation strategy in nonmetastatic germinoma patients should be minimum coverage of at-risk areas. In patients with nonmetastatic NGGCTs, the optimal radiation strategy needs further investigation.
A randomized, placebo-controlled, phase 2 trial of INBRX-109 in unresectable or metastatic conventional chondrosarcoma.
Authors: Sant P. Chawla, Garrett Thomas Wasp, Dale Randall Shepard, Jean-Yves Blay, Robin Lewis Jones, Silvia Stacchiotti, Peter Reichardt, Hans Gelderblom, Javier Martin-Broto, Brendan Eckelman, Michelle Darling, Vasily Andrianov, Anthony Paul Conley
Journal: Journal of Clinical Oncology (2022)

TPS11582 Background: Chondrosarcomas (CS) are the third most common type of primary bone cancer after myeloma and osteosarcoma. Conventional CS represent 85–90% of all cases and are typically treated with surgical resection. However, there are no approved systemic treatment options for patients with unresectable or metastatic conventional CS, and outcomes remain poor. INBRX-109 is a precision-engineered, tetravalent death receptor 5 (DR5) agonist antibody designed to overcome the limitations of earlier-generation agonists and exploit the tumor-specific cell death induced by DR5 activation. DR5 is one of two pro-apoptotic receptors for the trimeric tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Early clinical activity of INBRX-109 was observed in an ongoing phase 1 trial and warrants further investigation. INBRX-109 has been granted an FDA fast-track designation for conventional CS. Methods: This is a multicenter, randomized, blinded, placebo-controlled phase 2 study in patients with unresectable or metastatic conventional CS, measurable disease by RECIST 1.1, and radiologic disease progression within 6 months prior to screening. Any number of prior lines of therapy are allowed, except for prior DR5 agonists. Patients must be ≥18 years of age and have an ECOG performance status of 0/1 and have archival or fresh tissue available. Approximately 201 patients will be randomized (2:1) to INBRX-109 (3 mg/kg intravenously, every 21 days) or placebo, stratified by histologic grade (Grade 1/2 vs 3), isocitrate dehydrogenase (IDH)1 R132/IDH2 R172 status (wildtype vs mutation), and line of systemic therapy (none vs prior). Treatment will continue until disease progression/unacceptable toxicity. Patients treated with a placebo will have the option to cross over to INBRX-109 upon disease progression. The primary endpoint is progression-free survival (PFS) by independent radiology review. Secondary endpoints are overall survival, PFS by investigator assessment, quality of life, overall response rate, duration of response, disease control rate, safety, pharmacokinetics, and immunogenicity. Adverse events will be recorded and graded by NCI CTCAE Version 5.0. Median PFS of 7.0 months is projected for INBRX-109 and 4.0 months for placebo (corresponding hazard ratio of 0.571); INBRX-109 will be declared superior if the 1-sided p-value from the stratified log-rank test is &lt;0.025. More than 50 sites are planned across the US/Europe. The study is actively enrolling. Clinical trial information: NCT04950075.
Association postprandial hypertriglyceridemia, levels of leptin and carotid intima-media thickness in patients with coronary artery disease combined with nonalcoholic liver steatosis
Authors: M Grechanyk, O Kuryata
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: None. Main funding source(s): - Objective To estimate the frequency of postprandial hypertriglyceridemia (PPG), levels of leptin, carotid intima-media thickness in patients with coronary artery disease (CHD) combined with nonalcoholic liver steatosis (NALS). Methods We studied 61 patients with CHD in combination with NALS mean age 57,8±2,04 (group A) and 20 patients with CHD without NALS mean age 56,6±4,6 (group B). Patients with diabetes were excluded. Studied PPG, levels of leptin and carotid intima-media thickness. Results Revealed an increase in the level of triglycerides after fat load test in group A by 57% (from 2.27 [1.74; 2.77] mmol/l to 3.56 [2.60; 4.89] mmol/l), in the group B by 203% (s 1.24 [1.05; 1.86] mmol/l to 3.76 [1.64; 5.51] mmol/l). In patients in a group A identified the highest leptin levels 20,9 [12,3; 24,6] ng/ml than in a group B- 13,2 [7,3; 16,9] ng/ml, (p &amp;lt;0,02). Carotid wall thickness was lower in a group A (0,14±0,02 cm) than in a group B (0,16±0,01 cm, p =0,01). Frequency of exposure of atherosclerotic carotid plaques in a group A – 82%, was higher than in a group B – 64% (p &amp;lt;0,05). In group A unstable plaques found significantly more often (31%, p = 0,01), than in the control group B (8%). There was correlation between PPG and unstable plaques (r=0,75, p=0,03) in a subgroup with obesity grade 2. Conclusion The incidence of unstable atherosclerotic plaques of carotid arteries in the group with CAD and NALS was higher (34%) unlike patients with CAD without NALS (5%). It has been shown for the first time that under the conditions of the combined course of CAD with liver steatosis, an increase in body weight is associated with a reduced reaction of postprandial TG levels with an increase in leptin levels. According to the results of ROC analysis of significant predictors of liver steatosis in the group of patients with CAD were levels of leptin (AUC for leptin – 0.69 (0.56-0.82)).
Management of Patients With Resectable and Metastatic Non–Small Cell Lung Cancer
Authors: Jane Yanagawa, Gregory J. Riely
Journal: Journal of the National Comprehensive Cancer Network (2022)

For patients with resectable non–small cell lung cancer (NSCLC) as well as those with metastatic disease, there have been significant recent advances in therapies. In patients with resectable disease, new evidence supports use of neoadjuvant nivolumab + chemotherapy for eligible patients with resectable stage II–IIIA NSCLC. Separate data lead to the recommendation for adjuvant atezolizumab (after adjuvant chemotherapy) for eligible patients with completely resected stage II–IIIA NSCLC and PD-L1 expression ≥1%. Adjuvant osimertinib (± adjuvant chemotherapy) is an alternative for eligible patients with completely resected stage IB–IIIA NSCLC and EGFR mutations (exon 19 del or L858R). For patients with metastatic NSCLC, molecular testing is recommended for EGFR and BRAF mutations; MET exon skipping 14 alterations; ALK , ROS1 , RET , and NTRK1/2/3 gene arrangements; and KRAS G12C mutations. First-line targeted therapies are available for many of these targets and, in the second-line setting, there are new targeted agents for KRAS G12C mutations and EGFR exon 20 insertions.
Molecular design of a pathogen activated, self-assembling mechanopharmaceutical device
Authors: Andrew R. Willmer, Jiayi Nie, Mery Vet George De la Rosa, Winnie Wen, Steven Dunne, Gus R. Rosania
Journal: Journal of Controlled Release (2022)

Weakly basic small molecule drugs like clofazimine can be used as building blocks for endowing cells with unnatural structural and functional elements. Here, we describe how clofazimine represents a first-in-class mechanopharmaceutical device, serving to construct inert, inactive and stimulus responsive drug depots within the endophagolysosomal compartment of cells of living organisms. Upon oral administration, clofazimine molecules self-assemble into stable, membrane-bound, crystal-like drug inclusions (CLDI) that accumulate within macrophages to form a "smart" biocompatible, pathogen activatable mechanopharmaceutical device. Upon perturbation of the mechanism maintaining pH and ion homeostasis of these CLDIs, the inert encapsulated drug precipitates are destabilized, releasing bioactive drug molecules into the cell and its surrounding. The resulting increase in clofazimine solubility activates this broad-spectrum antimicrobial, antiparasitic, antiviral or cytotoxic agent within the infected macrophage. We present a general, molecular design strategy for using clofazimine and other small molecule building blocks for the cytoplasmic construction of mechanopharmaceutical devices, aimed at rapid deployment during infectious disease outbreaks, for the purpose of pandemic prevention.
Market determinants of commercial prices for intravenous chemotherapy infusions.
Authors: Michael Milligan, E. John Orav, Aaron Philip Mitchell, Miranda Lam
Journal: Journal of Clinical Oncology (2022)

1585 Background: Recent price transparency legislation mandated that hospitals across the country report their individually negotiated prices with insurers. Using this data, we sought to characterize the prices paid for standard intravenous (IV) chemotherapy infusions, and determine the hospital, regional, and market factors associated with higher prices. Methods: We utilized a database of U.S. hospital-reported price transparency data to characterize prices for the most commonly billed chemotherapy drug administration Common Procedural Terminology (CPT) codes— 96413 (initial IV chemotherapy infusion) and 96415 (additional hour of IV chemotherapy). We obtained standard charges and commercial prices negotiated with private payers from hospitals that directly administer chemotherapy. To assess variation in prices, we calculated the ratio of the 90 th percentile price to the 10 th percentile price among private payers in each hospital and among hospitals in each Hospital Referral Region (HRR). We performed multivariable linear regressions to assess hospital, regional, and market factors associated with higher prices. Results: A total of 1,458 hospitals reported at least one price for CPT code 96413 or 96415. Hospitals reported 1 chargemaster and a median of 18 (IQR: 8–35) commercial prices negotiated with different private payers. National median commercial prices for CPT codes 96413 and 96415 were $536.00 (IQR: $326.43-$784.63) and $175.06 (IQR: $98.28-$327.25), respectively. Within each hospital, the 90 th percentile commercial price was 2.2 times higher, on average, than the 10 th percentile price for CPT code 96413, and 2.8 times higher for 96415. Among different hospitals within each HRR, the median commercial price at the 90 th percentile hospital was 1.5 times higher than at the 10 th percentile for CPT code 96413, and 2.3 times higher for 96415. On multivariable analysis, higher prices for CPT code 96413 were observed at for-profit hospitals ($215.12 higher than government not-for-profit hospitals, 95% CI: $55.22-$429.61). Higher prices for CPT code 96415 were observed at hospitals with higher predicted practice costs ($35.79 for every 1% increase in the geographical practice cost index, 95% CI: $16.69-$54.87), and a lower disproportionate share percentage ($0.96 for every 1% decrease in DSH patient percentage, 95% CI: $0.08-$19.41). Conclusions: Commercial prices for commonly billed IV chemotherapy infusions demonstrate significant variability. Prices for identical infusions vary by a factor of 2 depending on which hospital or private payer a patient selects. While prices for CPT code 96415 are largely explained by the relative cost of care, prices for the more expensive 96413 appear to be driven by the profit-status of the hospital. Further study is required to characterize the implications of such high levels of price variability on access to care and overall healthcare costs.
Adjuvant abemaciclib for high-risk early breast cancer (EBC): Factors increasing the rate of treatment discontinuations in monarchE.
Authors: Sara M. Tolaney, Stephen R.D. Johnston, Ran Wei, Valerie AM Andre, Ashwin Shahir, Nadia Harbeck, Miguel Martin
Journal: Journal of Clinical Oncology (2022)

527 Background: Adjuvant abemaciclib plus endocrine therapy (ET) demonstrated clinically meaningful improvement in reducing the risk of recurrence in patients (pts) with HR+, HER2– high risk EBC. In monarchE, 25.6% pts discontinued abemaciclib before completing the 2-year treatment period due to reasons other than recurrence. This exploratory analysis evaluates the impact of baseline factors on time to discontinuation for abemaciclib-treated patients with an aim to identify pts at higher risk of discontinuation. Methods: Time to discontinuation(TTD) was defined as time from first dose to the discontinuation of abemaciclib or all treatment due to reasons other than recurrence. These exploratory analyses evaluated the association between TTD and baseline demographics, disease characteristics, and the extent of pre-existing medical comorbidities. Factors with p-value &lt;0.05 in the univariate Cox model were considered as potentially associated with TTD and then fitted into a multivariate Cox model with stepwise variable selection, with entry and retaining p-value threshold of 0.05. Discontinuation rates at selected timepoints (6-month, 12-month, 18-month, 24-month) within each subgroup were estimated using the Kaplan-Meier method. Results: The following variables were significantly associated with higher risk of discontinuation in the multivariate model: Age ≥65 yr, enrolled in North America or EU, ECOG PS=1, post-menopausal, 1-3 positive nodes, or 4 or more pre-existing comorbidities. The majority of discontinuations occurred within the first 6 months of the treatment period; thus, this timepoint was selected to estimate discontinuation rates for factors independently associated with TTD (Table). Complete results on discontinuation rates at other timepoints will be reported in the presentation. Conclusions: This exploratory analysis identified several factors associated with a greater risk of discontinuation. These results illustrate the importance of close monitoring and dose adjustments early on, particularly for patients with an increased risk of discontinuation prior to completing the 2-yr treatment period of abemaciclib. Clinical trial information: NCT03155997. [Table: see text]
Positive impact of oncology nurse navigation based on health insurance in head and neck cancer patients.
Authors: Christopher R Pallas, Danielle Boselli, Madison Kuch, Brittany Neelands, Daniel R. Carrizosa
Journal: Journal of Clinical Oncology (2022)

e18545 Background: Health disparity in squamous cell carcinoma of the head and neck (SCCHN) is well-recognized. Privately insured SCCHN patients are observed to have better outcomes, but underlying factors are poorly understood. Oncology nurse navigators (ONN) are a well-established role focused on optimizing cancer care and patient experience. The effects of ONN on bridging health disparities have not been demonstrated. We sought to characterize health and outcome disparities in patients diagnosed with oropharyngeal cancers and to assess if the implementation of ONN bridges gaps in health disparities. Methods: Patients aged &gt;18 diagnosed with node positive, non-metastatic oropharyngeal cancers at a large hybrid academic-community cancer center between June 2018 and September 2021 were analyzed retrospectively. Baseline demographic, socioeconomic and clinicopathologic factors including the frequency and percentage of patients receiving ONN were summarized. Clinical outcomes were assessed as a function of baseline factors and ONN. Overall survival (OS) and progression free survival (PFS) were evaluated with Kaplan Meier methods. Results: 184 patients were evaluated. Median age at diagnosis 62 (range 33-91). Median follow-up 24 months. The majority were HPV+ (73%). Navigation received in 64%. More males presented with cN1+ disease than females (57% v. 37%; p = 0.053). More Black patients presented with cN1+ disease than White patients (76% v. 50%; p = 0.017). More privately insured patients (92%) went to imaging after definitive treatment versus those with Medicaid (MD)/Self-pay (SP) (78%) or Medicare (MC)/Veteran’s affairs (VA) (78%) (p = 0.043), while more navigated patients went to imaging after definitive treatment than non-navigated patients (70% v. 40%; p = 0.003). Univariate modeling indicated clinical nodal stage, HPV status, race, and insurance status were associated with OS and PFS. In multivariable modeling adjusted for age, nodal stage, and HPV status, there was a disparity in OS associated with insurance type (MD/SP v. Private: HR 9.24, 95% CI = 2.34 to 36.41 and MC/VA; p = 0.004). There was a significant interaction of navigation and insurance type (p = 0.0157). In those not navigated, a difference in hazards exists between MD/SP or MC/VA compared with private insurance. This difference was not detected in those navigated. Similar interaction of navigation and insurance was noted in the analysis of PFS. Conclusions: We observed a disparity in patients with non-private insurance having an inferior PFS, OS and reduced rates of imaging after definitive treatment. An improved rate of post-treatment imaging was significantly associated with ONN. There was a trend towards benefit in outcomes for those receiving ONN but without private insurance suggesting that ONN may help mitigate disparities in the non-private insurance groups.
Politicians must behave differently and support NHS leaders to change cultures and improve patient care
Authors: Chris Ham
Journal: BMJ (2022)

Politicians must behave differently and support NHS leaders to change cultures and improve patient care Chris Ham co-chairThe late Harvard Business School professor, Clayton Christensen, once described hospitals as "some of the most managerially intractable institutions in the annals of capitalism." 1 Hardly surprising then that a stream of reports over the years have set out proposals for strengthening management in the NHS and social care. 2 The latest contribution by Gordon Messenger and Linda Pollard was spun by the government as the "biggest shake-up of health and social care leadership in a generation" ahead of its launch and its recommendations have already been accepted by Health and Social Care Secretary, Sajid Javid.
Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial
Authors: Sacha J Howell, Angela Casbard, Margherita Carucci, Kate Ingarfield, Rachel Butler, Sian Morgan, Magdalena Meissner, Catherine Bale, Pavel Bezecny, Sarah Moon, Chris Twelves, Ramachandran Venkitaraman, Simon Waters, Elza C de Bruin, Gaia Schiavon, Andrew Foxley, Robert H Jones
Journal: The Lancet Oncology (2022)

Capivasertib, an AKT inhibitor, added to fulvestrant, was previously reported to improve progression-free survival in women with aromatase inhibitor-resistant oestrogen receptor (ER)-positive, HER2-negative advanced breast cancer. The benefit appeared to be independent of the phosphoinositide 3-kinase (PI3K)/AKT/phosphatase and tensin homologue (PTEN) pathway alteration status of tumours, as ascertained using assays available at the time. Here, we report updated progression-free survival and overall survival results, and a prespecified examination of the effect of PI3K/AKT/PTEN pathway alterations identified by an expanded genetic testing panel on treatment outcomes.
Epidemiology and clinical impact of EGFR mutation in patients with lung cancer after radical surgical treatment.
Authors: Maciej Bryl, Magdalena Sielewicz, Bartłomiej Budny, Aldona Woźniak, Piotr Gabryel, Mariusz Kasprzyk, Aleksander Barinow-Wojewodzki, Cezary Piwkowski
Journal: Journal of Clinical Oncology (2022)

8552 Background: The epidemiology of epidermal growth factor receptor (EGFR) mutation in lung adenocarcinoma and its clinical impact are well-known. However, most studies have focused on advanced-stage inoperable cancer. Data on the frequency of EGFR mutation in surgically resected lung cancer are limited. Recent studies have shown a promising effect of Osimertinib in adjuvant settings. Hence, the need to estimate the target population in the real-world data. This study aimed to assess the occurrence of EGFR mutation in patients after radical surgical treatment of lung adenocarcinoma and explore its prognostic impact compared to EGFR negative group. Methods: This single-center retrospective analysis included the group of 732 consecutive Caucasian patients with histopathologically confirmed lung adenocarcinoma, evaluated for EGFR mutations expression, who underwent anatomical resection between January 2016, and December 2020. EGFR status was assessed by cobas EGFR mutation test v2. The frequency of EGFR mutations, disease-free survival (DFS) and overall survival (OS) in EGFR positive and EGFR negative groups were analyzed. Results: EGFR mutations were found in 65 surgical patients (8.9%) and did not differ from patients with advanced stages of lung adenocarcinoma (7.9%). EGFR mutations occurred more frequently in females than males, 48 out of 344 (14%) and 17 out of 388 (4.4%), respectively. Deletions within exon 19 and the L858R mutation in exon 21 constituted 49.2% and 24.6% of all mutations, respectively, while others comprised 26.2%. One case of L858R mutation coincided with T790M in exon 20 mutation. Detailed results divided by stages are presented in the Table. The occurrence of EGFR mutation had no significant influence on DFS and OS in patients after radical resection. Conclusions: The frequency of EGFR mutation in postoperative lung cancer was comparable to the occurrence in the general lung cancer population. EGFR mutation did not affect DFS and OS in patients after radical resection. [Table: see text]